Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of compounds 3f-j, are very high.     

Efficient microwave-assisted synthesis of 1-(1H-indol-1-yl)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents

New conazole antifungals, in the series of triazole alcohols 23a-d and 24a-e incorporating an indole moiety substituted at 5-position by halogens, a cyano or 4-methoxyphenyl group, have been synthesized by ring opening of corresponding oxiranes 15 and 16. These dihalogeno intermediates and their congeneers could be prepared in high yields by Corey-Chaykovsky reaction under microwave irradiation.     

[60]Fullerene adducts with 9-substituted anthracenes: mechanochemical preparation and retro Diels-Alder reaction

Three 9-substituted anthracene derivatives, that is, 9-hydroxymethylanthracene (2), 9-methoxymethylanthracene (3) and bis(9-anthrylmethyl) adipate (6), were chosen as the model compounds to evaluate the reactivity in their Diels-Alder reactions with [60]fullerene and in retro Diels-Alder reactions of the formed cycloadducts. Corresponding adducts 4, 5 and 7 were prepared in high yields under solvent-free conditions using high-speed vibration milling technique. In order to determine thermal stabilities of adducts 4, 5 and 7, their dissociations in the temperature range of 40-65 °C were investigated. Fitting the dissociation rates and temperatures to the Arrhenius equation gives the activation energies of 25.8, 21.8 and 24.9 kcal/mol for compounds 4, 5 and 7, respectively.     

Exceptional molecular architectures via cycloadditions to pyrenequinones

The thermal reaction of phencyclone (2) with a 1:1 mixture of 1,8-pyrenequinone (4) and 1,6-pyrenequinone (5) yields 2:1 adducts only of compounds 2 and 4. The observed polycyclic aromatic hydrocarbon 8 is formed via double Diels-Alder addition of 2 to 4, and the polycyclic ketone 9 arises from a combination of Diels-Alder and hetero-Diels-Alder reactions of 2 and 4. In contrast, Lewis acid-catalyzed reactions of 2, 4, and 5 give 2:1 adducts only of 2 and 5. The chief product, polycyclic diketone 10, is derived from a double hetero-Diels-Alder addition of 2 to 5. X-ray analysis of compound 8 shows it to be an exceptionally large polycyclic aromatic arch, and the X-ray structure of 10 reveals it to be a chiral molecular tweezer.     

Synthesis of indenes by ytterbium-catalyzed carboalkoxylation/Friedel-Crafts reaction of arylidenecyclopropanes with acetals

Ytterbium-catalyzed tandem carboalkoxylation/Friedel-Crafts reaction of arylidenecyclopropanes 1 with acetals 2 afforded the corresponding indene derivatives 3 in good to high yields. For example, in the presence of 10 mol % of Yb(OTf)₃ the reaction of 1-phenylbenzylidenecyclopropane 1a with the dimethyl acetals of benzaldehyde 2a, p-tolualdehyde 2b, and p-anisaldehyde 2c gave 1,3-diphenyl-2-(2-methoxyethyl)indene 3a, 2-(2-methoxyethyl)-3-phenyl-1-(p-tolyl)indene 3b, and 1-(p-anisyl)-2-(2-methoxyethyl)-3-phenylindene 3c in 82%, 80%, and 80% yields, respectively.     

Asymmetric 1,3-dipolar reactions of 3-sulfinylfuran-2(5H)-ones with 11H-dibenzo[b,e]azepine 5-oxide. Synthesis of pyrroloazepines via isoxazoloazepines

The addition of morphanthridine N-oxide (1) to homochiral 3-p-tolylsulfinylfuran-2(5H)-ones (2a and 2b) under mild conditions affords furoisoxazoloazepines (3a and 3b) in high yields and with complete regioselectivity. The π-facial and endo-selectivities are also complete from 2a, which yields anti-3a-endo as the only diastereoisomer, whereas cycloreversion determines that the anti-3b-endo adduct can be almost exclusively isolated from 2b. Proper manipulation of the furoisoxazoloazepines allows the synthesis of the optically pure isoxazoloazepines and pyrroloazepines.     

A Pd[0]-catalyzed Ullmann cross-coupling/reductive cyclization approach to C-3 mono-alkylated oxindoles and related compounds

The Pd[0]-catalyzed Ullmann cross-coupling of o-nitrohaloarenes 1a-e with the brominated heterocycles 2a-f delivers the expected products 3a-j in good to excellent yields. The reductive cyclization of such products, as well as N-acyl derivatives 3k, l, and m, has been investigated and provided the C-3 mono-substituted oxindoles 5a-d, f, g, k, and m, the direct reduction products 4i and j or indole 5l.     

A convenient synthesis of pyridine and 2,2′-bipyridine derivatives

α-Chloro-α-acetoxy-β-keto-esters 9 were readily prepared from β-keto-esters 6 in good overall yields. These compounds reacted as α,β-diketo-ester equivalents 2 with amidrazones 1 yielding triazines 3, generally in good yields. Picolinates 10 provided an alternative source of α,β-diketo-ester equivalents 2 when treated with copper(II) acetate. A ‘one-pot’ reaction of the α,β-diketo-ester equivalents 2 with amidrazones 1 in the presence of 2,5-norbornadiene 5 in boiling ethanol yielded the pyridines 4 and 2,2′-bipyridines 4 (R¹=2-pyridyl) directly without the need to isolate the corresponding triazines 3. Triazine 3c reacted with the aza-dienophiles 13 and 17 affording the products 16 and 18, respectively, in good yields.     

Functionalized esters as bis-electrophiles in a silicon-induced domino synthesis of annulated carbocycles

The reaction of silyl-substituted carbanion 1b with arene-1,2-dicarboxylates 6, 15 yields indenone derivatives 11, 16 in a domino process involving silyl C→O migration and elimination. However, in a competing pathway, the initial addition of 1b leads to lactone formation (8, 17). Substrates 26, 38 containing an ester group and a bromine substituent react with 1b under substitution of the halogen not allowing silyl migration. But desilylation with TBAF gives reactive carbanions providing benzo-annulated cycloalkanones 29, 40.     

Manganese(III)-based oxidation of 1,2-disubstituted pyrazolidine-3,5-diones in the presence of alkenes

The manganese(III)-catalyzed aerobic oxidation of 1,2-disubstituted pyrazolidine-3,5-diones 1 in the presence of alkenes 2 gave the corresponding pyrazolidinediones 3 which were doubly hydroperoxyalkylated at the 4-position in high yields. On the other hand, pyrazolidinediones 1 were oxidized with manganese(III) acetate in the presence of alkenes 2 at elevated temperature to produce the 4,4-bis(alkenyl)pyrazolidinediones 4 in good yields instead of the pyrazolidine-fused dihydrofuran analogue IV. A similar cerium(IV)-mediated oxidation of pyrazolidinedione 1a with an alkene 2a afforded the doubly 4-methoxyethylated derivative 5. The stability of the free hydroperoxyl group and the reaction pathway for the aerobic and the metal-mediated oxidation reactions were also discussed.     

Stereoselective intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes: a novel approach for the synthesis of complex annulated uracils

The intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes 4, obtained from salicylaldehyde 1 via O-allylation followed by Knoevenagel condensation with barbituric acids 3 in the presence of hydrochloric acid as catalyst, affords the tetracyclic uracil derivatives 5 and 6 in a stereoselective manner and high overall yields.     

Environmentally benign syntheses of flavanones

Mild and environmentally benign methods for the syntheses of flavanones are described. The reaction of o-hydroxyacetophenones (1) and benzaldehydes (2) in water in the presence of DABCO at room temperature gave 3-hydroxy-1-(2-hydroxylphenyl)-3-arylpropan-1-ones (3a-i) as intermediates. Followed by an intramolecular dehydration of the 3a-i with the modified Mitsunobu’s reaction, the target flavanones (4a-i) were obtained. Moreover, the reaction of 1 and 2 at the same conditions but at reflux gave flavanones in one pot with good yields.     

Studies on uracils: a facile one-pot synthesis of oxazino[4,5-d]-, pyrano[2,3-d]-, pyrido[2,3-d]- and pyrimido[4,5-d]pyrimidines using microwave irradiation in the solid state

N,N-Dimethyl-5-formylbarbituric acid 1 reacts with maleimide 2 and phenyl isocyanate/phenyl isothiocyanate 4 under microwave-assisted conditions in the solid phase to afford pyrano[2,3-d]pyrimidines 3 and oxazino[4,5-d]pyrimidines 5 in excellent yields. Under identical conditions, N,N-dimethyl-6-amino-5-formyluracil 6 reacts with 2 and 4 to give pyrido[2,3-d]pyrimidine derivative 7 and pyrimido[4,5-d]pyrimidines 8 in high yields.     

Copper-catalyzed dimerization of chromium Fischer carbene complexes: synthesis of dialkoxytrienes and their Nazarov-type cyclization to 2-alkoxy-2-cyclopentenones

Fischer carbene complexes 1 underwent a clean ligand dimerization reaction yielding functionalized olefins and trienes 4 in the presence of copper (I) catalysts. If treated with trifluoroacetic acid (TFA), trienes 4c, d, f undergo a cyclization process (Nazarov reaction) which furnishes cyclopentenone derivatives 6c, d, 7c, d and 8 in good yields. Finally, the Fischer aminocarbene 9 efficiently cyclodimerizes to the substituted arene 10 in the presence of CuBr.     

Stereocontrolled synthesis of hydroxyethylamine isosteres via chiral sulfoxide chemistry

A novel synthesis of enantiopure hydroxyethylamine isosteres 1 has been developed. Reaction of lithiated β-sulfinylethylamines 3 with N-Cbz-imines generated in situ from α-amino-sulfones 4 afforded in good to excellent yields and moderate stereocontrol the 2-sulfinyl-1,3-diamines 2. The latter were submitted to the nonoxidative Pummerer reaction (NOPR) in CH₂Cl₂, that produced the target compounds 1 in very good yields with inversion of configuration. In some cases, the use of acetonitrile as solvent resulted in a double-inversion pathway, leading for example to the oxazolidinone 5. The total synthesis of an epimer of Saquinavir has been achieved by this method.     

Palladacycle as highly efficient catalyst for ring opening of oxabicyclic alkenes with organozinc halides

Ring opening reaction of oxabicylic alkenes 4 with in situ prepared organozinc halides 5 was catalyzed by palladacycle 3 with high efficiency. Good yields of the corresponding 1,2-dihydronaphth-1-ols (6) were provided when as low as 0.05 mol% of palladacycle 3 was used. ³¹P NMR study showed that the skeleton of 3 remained intact in the reaction, which implied that palladacycle 3 did not serve as a catalyst precursor but a catalyst in the reaction.     

One-pot synthesis of malononitriles by free radical reactions of ylidenemalononitrile with Et3B and iodoalkane in a water-ether biphase medium

The one-pot synthesis of malononitrile derivatives 4, 6, and 7 in moderate to high yields by the reaction of ylidenemalononitriles 3, prepared in situ from carbonyl compounds 1 and malononitrile 2 in the presence of ammonium acetate in aqueous solution at 50-60 °C, with Et₃B or RI 5/Et₃B in a water-diethyl ether biphase medium under an atmosphere of room temperature is reported. The reaction of Et₃B with adamantyl iodides 8 and 10 under similar conditions gave 9 and 11 in high yields, respectively. However, low yields of the monoalkylated combined with dialkylated malonates 14 were obtained when benzaldehyde 1a was condensed with dimethylmalonate 12 followed by parallel free radical treatment in benzene solution.     

Cycloaddition reactions of 3-fluorobutenone

3-Fluorobutenone (8) reacted as a dienophile with several dienes 9, 11, 13, 15, 17 to give cycloaddition products in moderate yields. The regio- and stereoselectivity of the reactions are given. Compound 8 is slightly less reactive than methyl vinyl ketone.     

Facile generation method for conjugated allenyl esters based on retro-Dieckmann-type ring-opening reactions

α-Alkynyl-α-ethoxycarbonyl cyclopentanones 1a-c and cyclohexanones 2a-c were readily synthesized by the reaction of ethyl 2-oxocyclopentanonecarboxylate 6 and ethyl 2-oxocyclohexanonecarboxylate 7 with alkynyllead triacetates 5a-c obtained from lithium acetylides 4a-c and lead tetraacetate. Treatment of 1a-c and 2a-c with 1 N KOH in THF or with n-Bu₄N⁺OEt⁻ in EtOH and THF gave the corresponding conjugated allenyl esters 8a-c, 9a-c, 10a-c, and 11a-c in good to excellent yields, respectively.     

Synthesis and substitution reactions of β-alkoxyvinyl bromodifluoromethyl ketones

β-Alkoxyvinyl bromodifluoromethyl ketones 1a, 1b and 1c were synthesized by the reaction of bromodifluoroacetic anhydride with appropriate vinyl ethers in high yields. The acyclic enone 1a reacted with amines to give the corresponding β-aminovinyl bromodifluoromethyl ketones 2 in good yields. The reaction of 1a with electrophilic reagent ICl yielded α-iodoenone 4. The substitution reaction of the cyclic enones 1b and 1c with thio-nucleophiles gave the corresponding difluoromethylene thioethers 6. The three-component reactions of 2 with primary amines and formaldehyde gave multifunctional 1,2,3,4-tetrahydropyrimidine 3 in moderate yields.